The invention relates generally to the photoconversion of steroids on solid catalytic surfaces and more particularly to controlling the stereochemistry of the photoconversion reaction by proper selection of a microreactor.
Photochemical isomerization of steroids are important in the industrial synthesis of commercial products. For example, the photoisomerization of 7-dehydrocholesterol (7-DHC) yields previtamin D.sub.3, which can be converted by conventional methods, such as by thermal rearrangement, to vitamin D.sub.3. Vitamin D.sub.3 has many important uses. For example, vitamin D.sub.3 can be used as an additive to milk and in animal feeds to prevent rickets.
A similar type of photoisomerization is carried out to produce 1.alpha.,25-dehydroxyvitamin D.sub.3. This is the actual active form of vitamin D.sub.3 that is responsible for regulating calcium metabolism. The synthesis of dydrogesterone, developed by Philips-Duphar, also includes a photoisomerization of a steroidal intermediate. (M. Fischer, Angew. Chem. Int. Ed. Engl. 17, 16-26 (1978).)
The photoisomerization of steroids is conventionally carried out in solution. The conventional photolysis of 7-dehydrocholesterol initially gives the desired previtamin D.sub.3. However, previtamin D.sub.3 also absorbs light of the same region of the electromagnetic spectrum as does 7-dehydrocholesterol. This leads to a second undesirable photo-induced isomerization in which tachysterol is formed.
There have been many attempts to deal with the unwanted formation of tachysterol. However, these attempts have been less than completely satisfactory. For example, one approach is to stop irradiation after 30-50% conversion to previtamin D.sub.3 and then isolate previtamin D.sub.3. However, this procedure adds considerable expense to the production of vitamin D.sub.3.
Another approach is to use consecutive irradiations with different wavelengths. An initial high energy irradiation of 7-dehydrocholesterol gives a mixture of previtamin D.sub.3 and tachysterol. A second lower energy radiation then converts some of the tachysterol back to previtamin D.sub.3. This is also not fully satisfactory and leads to a higher percentage of lumisterol in the product (V. Malatesta, C. Willis and P. A. Hackett, J. Am. Chem. Soc., 103, 6781-2-3, (1981) and U.S. Pat. No. 4,388,242). The contents of U.S. Pat. No. 4,388,242 are incorporated herein, by reference.
Still another approach includes the addition of xanthenone analog sensitizers to the steroidal reactant, followed by irradiation with low energy wavelength light. This leads to decreased amounts of tachysterol in the product mixture (H. J. Hansen and K. Pfoertner, European Patent 130509, 1985). A second irradiation at lower energy with anthracene as an initiator also minimizes the amount of tachysterol present in the reaction mixture (See, U.S. Pat. No. 4,686,023, the contents of which are incorporated herein by reference). However, the use of sensitizers and initiators are generally undesirable because they complicate the purification process.
Accordingly, it is desirable to provide an improved method of conducting photoconversion reactions of steroids with greater control of the reaction product.